TNF and anti-TNF agents in Behçet's disease

The rapid response and effectiveness of anti-TNF agents in the treatment of many immune mediated inflammatory disorders draws comparison to the response of rheumatoid arthritis to cortisone, first witnessed over 50 years ago by Philip Hench and colleagues at the Mayo Clinic. It is now known that many of the anti-inflammatory effects of corticosteroids are due to their inhibition of TNF production. A new dimension of efficacy is possible with TNF agents, however, in that inhibition of disease progression is now possible. Might these agents be considered the corticosteroids of the new millennium? Like rheumatoid arthritis and Crohn's disease, Behçet's disease is believed to be associated with a Th1-mediated immune response. Increased levels of TNF-α are found in Behçet's disease and has provided support for the empiric use of anti-TNF-α therapies used in a number of published cases and small case series.

Hassard (2001) reported rapid and dramatic improvement in gastrointestinal and extraintestinal symptoms and findings of the disorder after treatment with infliximab. Similar response was seen in two other patients treated by Travis (2001). This experience was followed by the report of Robertson (2001) of a patient free of oral and genital ulcerations for the first time in 10 years after three infusions of infliximab. Remission of mucocutaneous symptoms for one year followed two infusions of infliximab in a patient previously uncontrolled by multiple immunosuppressive agents (Goossens, 2001). Mucocutaneous lesions remitted with infliximab in a patient with Behçet's disease associated with rheumatoid arthritis (Rozenbaum, 2002). At EULAR 2002, Turkish investigators reported the results of the first double-masked, placebo-controlled study (n = 40) of anti-TNF therapy with etanercept in mucocutaneous Behçet's disease (Melikoglu, 2002). This agent suppressed disease manifestations with resurgence after the drug was discontinued. Additional recent reports of anti-TNF therapies in Behçet's disease were presented at several international meetings.

The experience with anti-TNF-α treatments for the ocular manifestations of Behçet's disease has been growing and very positive. Sfikakis (2001) reported the benefits of infliximab in five patients with panuveitis in Behçet's disease. This included two patients treated with infliximab therapy without an increase in conventional treatment. At the ACR meeting in 2002 these Greek investigators reported successful monotherapy with infliximab in acute ocular inflammation in Behçet's disease in 14 patients. The authors suggested that the dramatic and rapid response in these patients would favor the use of this agent over conventional therapy. Positive responses to anti-TNF agents in ocular Behçet's disease have been documented in numerous case reports in the literature or presentations at international meetings.

Significant differences exist between currently available anti-TNF-α agents, including mechanism of TNF-α inhibition, avidity, half life, immunogenicity, ability to bind lymphotoxin (TNF-β), ability to bind membrane bound TNF-α, as well as the mode and frequency of administration. One or more of these differences may account for the variable efficacy of these agents in certain diseases, such as Crohn's disease, and the variable side-effect profile of these drugs. We believe that it is appropriate to study all available agents, including adalimumab, for their efficacy and safety in Behçet's disease. The efficacy of these new biologic agents for the more serious manifestations of Behçet's disease, in particular, should be investigated.